Nanofluidic delivery system

Abstract

Painless, non-invasive nanofluidic delivery systems useful for the delivery of therapeutically active agents, GRAS agents, sterile fluids and inert fillers through epithelial membranes are described. The painless, non-invasive delivery system delivers a therapeutic agent via a micro-syringe-based assembly. The painless, non-invasive delivery system may also have a vehicle, which facilitates the absorption of the therapeutic agents by altering its absorption rate at the site of administration. Also disclosed is a method and components of the delivery system to administer therapeutic agents in a consistent, predictable and reproducible manner. Certain compositions may facilitate the delivery of different agents without altering the agents from their current or previous form.

What is claimed is: 
     
         1 . Apparatus for delivering an active agent to a patient, said apparatus comprising:
 a carrier comprising a flexible concave member; and   a syringe mounted to said flexible concave member, said syringe comprising:
 a chamber having a proximal end and a distal end and containing an active agent to be delivered to a patient, wherein said distal end of said chamber comprises a wafer substrate having a plurality of openings formed therein and having plurality of hollow fibers extending distally therefrom; 
 a locking mechanism disposed in telescoping relation with said chamber; 
 a support band disposed in telescoping relation with said locking mechanism; 
 one or more retention mechanisms that releasably secure said locking mechanism to said support band; and 
 a plunger having a proximal end and a distal end and a telescoping rod disposed therebetween, wherein said distal end comprises a plunger disc disposed in said chamber and wherein said proximal end of said plunger comprises a comfort top that communicates with said flexible concave member of said carrier; and 
 a spring disposed between said comfort top and said proximal end of said chamber so as to bias said comfort top proximally away from said proximal end of said chamber; 
   wherein when a distally-directed force is applied to said comfort top, said force overcomes said one or more retention mechanisms, moves said chamber and said locking mechanism as a unit distally and telescopically relative to said support band thereby deploying said hollow fibers distally beyond said support band and into the patient, and further wherein continued application of the distally-directed force to said plunger top overcomes the proximal bias of said spring and causes said plunger disc to move distally and push the active agent out of said chamber through said openings in said wafer substrate, through said hollow fibers and into the patient.   
     
     
         2 . Apparatus according to  claim 1  wherein a peel-away strip extends across the bottom of flexible concave member thereby enclosing said syringe inside said concave member. 
     
     
         3 . Apparatus according to  claim 2  wherein the volume of the concavity not occupied by said syringe is filled with a gel. 
     
     
         4 . Apparatus according to  claim 1  wherein said hollow fibers are provided in such numbers and in closely-spaced relation to one another so as to create a self-supporting meta-structure. 
     
     
         5 . Apparatus according to  claim 1  wherein said hollow fibers comprise carbon nanotubes. 
     
     
         6 . Apparatus according to  claim 1  wherein said hollow fibers comprise tubular structures. 
     
     
         7 . Apparatus according to  claim 1  wherein said one or more retention mechanisms comprise shear tabs. 
     
     
         8 . Apparatus according to  claim 1  wherein the plunger disc is formed of silicone. 
     
     
         9 . Apparatus according to  claim 1  wherein each of said plurality of hollow fibers is long enough to penetrate the skin of the patient and narrow enough to avoid causing pain to the patient. 
     
     
         10 . Apparatus according to  claim 1  wherein a sufficient number of hollow fibers are provided so as to deliver the desired quantity of the active agent from said chamber to the patient within a desired time. 
     
     
         11 . A method for delivering an active agent to a patient, said method comprising:
 providing apparatus for delivering an active agent to a patient, said apparatus comprising:
 a carrier comprising a flexible concave member; and 
 a syringe mounted to said flexible concave member, said syringe comprising:
 a chamber having a proximal end and a distal end and containing an active agent to be delivered to a patient, wherein said distal end of said chamber comprises a wafer substrate having a plurality of openings formed therein and having plurality of hollow fibers extending distally therefrom; 
 a locking mechanism disposed in telescoping relation with said chamber; 
 a support band disposed in telescoping relation with said locking mechanism; 
 one or more retention mechanisms that releasably secure said locking mechanism to said support band; and 
 a plunger having a proximal end and a distal end and a telescoping rod disposed therebetween, wherein said distal end comprises a plunger disc disposed in said chamber and wherein said proximal end of said plunger comprises a comfort top that communicates with said flexible concave member of said carrier; and 
 a spring disposed between said comfort top and said proximal end of said chamber so as to bias said comfort top proximally away from said proximal end of said chamber; 
 
 wherein when a distally-directed force is applied to said comfort top, said force overcomes said one or more retention mechanisms, moves said chamber and said locking mechanism as a unit distally and telescopically relative to said support band thereby deploying said hollow fibers distally beyond said support band and into the patient, and further wherein continued application of the distally-directed force to said plunger top overcomes the proximal bias of said spring and causes said plunger disc to move distally and push the active agent out of said chamber through said openings in said wafer substrate, through said hollow fibers and into the patient; 
   disposing said carrier against the skin of the patient at a desired location;   applying a distally-directed force to said comfort top to overcome said one or more retention mechanisms, whereby to move said chamber and said locking mechanism as a unit distally and telescopically relative to said support band thereby deploying said hollow fibers into the skin of the patient;   continuing the application of said distally-directed force to move said plunger disc distally so as to push the active agent out of said chamber through said openings in said wafer substrate, through said hollow fibers and into the patient.   
     
     
         12 . Apparatus for delivering an active agent to a patient, said apparatus comprising:
 a flexible carrier comprising a concavity; and   a syringe mounted within said concavity of said flexible carrier, said syringe comprising:
 a hollow base comprising a distal end and a proximal end; 
 a cap movably mounted to said proximal end of said hollow base; 
 a spring disposed between said distal end of said hollow base and said cap, said spring being configured to proximally bias said cap; 
 a wafer substrate comprising a distal surface and a proximal surface, and a plurality of openings extending between said distal surface and said proximal surface, said wafer substrate being movably disposed within said hollow base; 
 a plurality of nano-needles extending distally from said distal surface of said wafer substrate, wherein each of said nano-needles comprises a distal end and a proximal end, and a lumen extending therebetween, and further wherein said each lumen of each of said plurality of nano-needles is aligned with said openings formed in said wafer substrate; 
 a rod having a distal end and a proximal end, wherein said distal end of said rod is mounted to, and extends between, said wafer substrate and said cap; 
 a needle support plate mounted to the distal end of said hollow base, said needle support plate comprising a plurality of openings sized to receive a plurality of nano-needles therein; 
 a timing ring having a distal end and a proximal end, and a plunger disc mounted to said distal end of said timing ring, wherein said timing ring and said plunger disc are disposed coaxially about said rod intermediate said cap and said wafer substrate, whereby to define a chamber between said plunger disc and said wafer substrate for containing the active agent which is to be delivered to a patient, and further wherein said timing ring is configured to selectively move longitudinally relative to said rod and is configured to selectively rotate relative to said rod; 
 a torsional spring disposed between said cap and said distal end of said timing ring; 
 a locking ring mounted to said timing ring and to said hollow base, said locking ring being configured to selectively permit said timing ring to rotate relative to said rod; 
   wherein when said cap is moved distally, (i) said wafer substrate moves distally so as to project said plurality of nano-needles through said openings formed in said needle support plate and into the patient, and (ii) said locking ring releases said timing ring, whereby to allow said torsional spring to bias said timing ring and said plunger disc distally and thereby force the active agent contained in said chamber into said openings formed in said substrate, through said lumens of said plurality of nano-needles, and into the patient.   
     
     
         13 . Apparatus according to  claim 12  wherein a peel-away strip extends across the bottom of flexible carrier sealing said syringe within said concavity. 
     
     
         14 . Apparatus according to  claim 13  wherein the volume of the concavity not occupied by said syringe is filled with a gel. 
     
     
         15 . Apparatus according to  claim 12  further comprising a spring-biased needle guide plate disposed between said distal surface of said wafer substrate and said needle support plate, wherein said spring-biased needle guide plate comprises a plurality of openings sized to receive said plurality of nano-needles so as provide lateral support thereto. 
     
     
         16 . Apparatus according to  claim 12  wherein said nano-needles comprise carbon nanotubes. 
     
     
         17 . Apparatus according to  claim 12  wherein said nano-needles comprise tubular structures. 
     
     
         18 . Apparatus according to  claim 12  further comprising a cycle indicator mounted to said locking ring for indicating the cycle status of said syringe. 
     
     
         19 . Apparatus according to  claim 12  wherein each of said plurality of nano-needles is long enough to penetrate the skin of the patient and narrow enough to avoid causing pain to the patient. 
     
     
         20 . Apparatus according to  claim 12  wherein a sufficient number of nano-needles are provided so as to deliver the desired quantity of the active agent from said chamber to the patient within a desired time. 
     
     
         21 . A method for delivering an active agent to a patient, said method comprising:
 providing apparatus for delivering an active agent to a patient, said apparatus comprising:
 a flexible carrier comprising a concavity; and 
 a syringe mounted within said concavity of said flexible carrier, said syringe comprising:
 a hollow base comprising a distal end and a proximal end; 
 a cap movably mounted to said proximal end of said hollow base; 
 a spring disposed between said distal end of said hollow base and said cap, said spring being configured to proximally bias said cap; 
 a wafer substrate comprising a distal surface and a proximal surface, and a plurality of openings extending between said distal surface and said proximal surface, said wafer substrate being movably disposed within said hollow base; 
 a plurality of nano-needles extending distally from said distal surface of said wafer substrate, wherein each of said nano-needles comprises a distal end and a proximal end, and a lumen extending therebetween, and further wherein said each lumen of each of said plurality of nano-needles is aligned with said openings formed in said wafer substrate; 
 a rod having a distal end and a proximal end, wherein said distal end of said rod is mounted to, and extends between, said wafer substrate and said cap; 
 a needle support plate mounted to the distal end of said hollow base, said needle support plate comprising a plurality of openings sized to receive a plurality of nano-needles therein; 
 a timing ring having a distal end and a proximal end, and a plunger disc mounted to said distal end of said timing ring, wherein said timing ring and said plunger disc are disposed coaxially about said rod intermediate said cap and said wafer substrate, whereby to define a chamber between said plunger disc and said wafer substrate for containing the active agent which is to be delivered to a patient, and further wherein said timing ring is configured to selectively move longitudinally relative to said rod and is configured to selectively rotate relative to said rod; 
 a torsional spring disposed between said cap and said distal end of said timing ring; 
 a locking ring mounted to said timing ring and to said hollow base, said locking ring being configured to selectively permit said timing ring to rotate relative to said rod; 
 
   wherein when said cap is moved distally, (i) said wafer substrate moves distally so as to project said plurality of nano-needles through said openings formed in said needle support plate and into the patient, and (ii) said locking ring releases said timing ring, whereby to allow said torsional spring to bias said timing ring and said plunger disc distally and thereby force the active agent contained in said chamber into said openings formed in said substrate, through said lumens of said plurality of nano-needles, and into the patient;   disposing said flexible carrier against the skin of the patient at a desired location;   applying a distal force so as to move said cap distally, whereby to (i) advance said plurality of nano-needles into the skin of the patient, and (ii) force the active agent contained in said chamber into said openings formed in said substrate, through said lumens of said plurality of nano-needles, and into the patient; and   allowing said cap to move proximally under the power of said spring disposed between said distal end of said hollow base and said cap, whereby to move said wafer substrate and said plurality of nano-needles proximally, whereby to withdraw said nano-needles from the skin of the patient.   
     
     
         22 . A nano-needle comprising a plurality of carbon nanotubes having a matrix material filling the interstitial spaces between said carbon nanotubes. 
     
     
         23 . A method for making a nano-needle comprising a plurality of carbon nanotubes, said method comprising:
 providing a wafer substrate having one or more openings extending therethrough;   depositing a catalyst around the periphery of said one or more openings extending through said wafer substrate;   activating said catalyst so that said catalyst forms islands around the periphery of said one or more openings;   growing a plurality of carbon nanotubes from said islands;   applying a matrix material to the interstitial spaces between said carbon nanotubes so as to form a hollow nano-needle having a diameter that is roughly defined by the periphery of said one or more openings.